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Local recurrence model of malignant pleural mesothelioma for investigation of intrapleural treatment

Opitz, Isabelle ; Lardinois, Didier ; Arni, Stephan ; Hillinger, Sven ; Vogt, Peter ; Odermatt, Bernhard ; Rousson, Valentin ; Weder, Walter

In: European Journal of Cardio-Thoracic Surgery, 2007, vol. 31, no. 5, p. 772-778

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    Titre
    • Local recurrence model of malignant pleural mesothelioma for investigation of intrapleural treatment
    Auteur
    • Opitz, Isabelle. Division of Thoracic Surgery, University Hospital Zurich, Switzerland
    • Lardinois, Didier. Division of Thoracic Surgery, University Hospital Zurich, Switzerland
    • Arni, Stephan. Division of Thoracic Surgery, University Hospital Zurich, Switzerland
    • Hillinger, Sven. Division of Thoracic Surgery, University Hospital Zurich, Switzerland
    • Vogt, Peter. Institute of Surgical Pathology, Department Pathology, University Hospital Zurich, Switzerland
    • Odermatt, Bernhard. Institute of Surgical Pathology, Department Pathology, University Hospital Zurich, Switzerland
    • Rousson, Valentin. Institute of Biostatistics, University of Zurich, Switzerland
    • Weder, Walter. Division of Thoracic Surgery, University Hospital Zurich, Switzerland
    Type de document
    • Postprint
    Langue
    • Inglese
    Publié dans
    • European Journal of Cardio-Thoracic Surgery, 2007, vol. 31, no. 5, p. 772-778. Elsevier Science B.V.
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:298606
    Summary
    Objective: Local recurrence remains a major problem in the treatment of malignant pleural mesothelioma. The aim of the underlying study was to establish a standardised local recurrence model in rats which enables to study different intrapleural therapies. Materials and methods: Fifty microlitre containing 1×106 cells of a syngeneic rat malignant mesothelioma cell line (II-45), established from mesothelioma in Fischer 344 rats exposed to asbestos, were inoculated subpleurally via a left-sided thoracotomy. Tumour size was assessed 6 days later and the tumour nodule completely resected. Evaluation of recurrence at the resection site was performed after 10 days (n=6) and 6 days (n=6). The recurrent nodule was histopathologically confirmed. In a second experiment, this new recurrence model was evaluated for the effect of intrapleural therapy with different agents: 4ml of cisplatin-solution (100mg2/kg BW), cisplatin combined with the fibrin-based sealant Vivostat®, 4ml taurolidine 2%, repeated injection of 1μg of the chemokine CCL-19 at the tumour site and 4ml povidone-iodine in a dilution 1:10. In a control group, the chest cavity was filled with 4ml 0.9% NaCl. The primary endpoint was the extent of tumour recurrence. Results: Six days after inoculation, all animals presented a standardised tumour nodule at the injection site of a mean diameter of 5.1 (±0.8)mm. Evaluation of the recurrence after 10 days showed a relapse directly at the resection site, but additional tumour nodules on the ipsi- and contralateral chest wall were found and histologically confirmed. The animals that were sacrificed 6 days after resection of the tumour nodule showed a recurrence only at the resection site with no macroscopic or microscopic evidence of other tumour. Resection of the tumour nodule combined with intrapleural application of the different agents lead to clear reduction of recurrence. The strongest effect was observed after intrapleural application of cisplatin-Vivostat® with significant decrease of the longest, widest and thickest diameter of the recurrence. Conclusions: With this new recurrence model for investigation of malignant pleural mesothelioma in rats, we were able to investigate new intrapleural therapies after pneumonectomy. The intrapleural application of cisplatin-Vivostat® significantly reduced the extent of local recurrence